I. Introduction to CHAPLE Disease
CHAPLE (Complement Hyperactivation, Angiopathic thrombosis, and Protein-Losing Enteropathy) disease, also known as CD55 deficiency, is a rare genetic condition that affects the immune system. It is an ultra-rare recessive condition caused by loss-of-function mutations in the CD55 gene, which is translated into the protein called decay-accelerating factor (DAF). There are fewer than 100 individuals worldwide known to have the disease. In the U.S., fewer than 10 patients with CHAPLE disease have been identified. [Regeneron, 2023]
It is characterized by severe protein-losing enteropathy (the loss of proteins from the intestines) leading to hypoproteinemia. The main symptoms of CHAPLE disease include: [Ozen, 2017]
➢ Gastrointestinal symptoms: These can include abdominal pain, nausea, vomiting, diarrhea, and loss of appetite.
➢ Weight loss: Due to the gastrointestinal symptoms and malabsorption.
➢ Edema: This is swelling caused by excess fluid trapped in your body’s tissues.
➢ Malabsorption: People with CHAPLE disease also have chronic malabsorption, which causes deficiencies in iron, ferritin, calcium, magnesium, folate, vitamin D and vitamin B12.
Additionally, individuals with CHAPLE disease are prone to experiencing lung infections and recurrent blood clots. These blood clots can occur in various blood vessels, including veins and arteries, and can lead to serious complications. This condition usually manifests in childhood and can be life-threatening.
The hyperactivation of the complement system, a part of the immune system responsible for clearing pathogens and damaged cells, is a characteristic feature of CHAPLE disease. [Dho, 2018] The excessive activation of the complement system contributes to inflammation, tissue damage, and the development of blood clots.
CHAPLE disease is ultra-rare making it challenging to diagnose, however non-functional or low levels of DAF protein could provide a clue. Genetic testing could confirm the presence of mutations in the CD55 gene that prevent functional DAF protein production. A diagnostic test that takes into account CD55 status at the DNA and protein level has been patented. [Lenardo, 2021]
Until recently, treatment for CHAPLE disease was mainly supportive and focused on managing symptoms, such as controlling gastrointestinal issues and preventing infections. Consulting with a healthcare professional is essential for individuals suspected of having CHAPLE disease to receive appropriate care and management.
II. Recent Treatment Innovations
Very recent advances in the understanding of CHAPLE Disease have enabled new proactive treatment options. [Lavelle, 2017]
Eculizumab
Eculizumab is a recombinant humanized monoclonal antibody that specifically binds to the terminal complement component 5, or C5, which acts at a late stage in the complement cascade. When activated, C5 is involved in activating host cells, thereby attracting pro-inflammatory immune cells, while also destroying cells by triggering pore formation. [Eculizumab, 2020]
Eculizumab has been used off-label and shown to provide a dramatic benefit in CHAPLE Disease. [Prabhu, 2022] Thus Eculizumab provides a potent treatment option, however, one serious warning associated with Eculizumab is the risk of meningococcal infections, which may rapidly become life-threatening or fatal if not recognized and treated early. Therefore, it’s recommended to immunize patients with a meningococcal vaccine at least 2 weeks prior to administering the first dose of Eculizumab [Drugscom, 2022]
Pozelimab-bbfg
Pozelimab-bbfg, also known as Veopoz, is a treatment for CHAPLE disease in adult and pediatric patients 1 year of age and older, which was approved by the FDA on August 18, 2023. [CDER, 2023]
Pozelimab-bbfg is a fully human monoclonal antibody designed to block the activity of complement factor C5, a protein involved in complement system activation. By blocking the cleavage of C5 into C5a (anaphylatoxin) and C5b, Pozelimab-bbfg inhibits terminal complement activation, thereby blocking the formation of the membrane-attack complex (C5b-C9...
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